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Updated: Sep 6, 2025
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Suppressive effect of therapeutic antibiotic regimen on antipneumococcal Th1/Th17 responses in neonatal mice
Sudhanshu Shekhar1, Navdeep K Brar2, Fernanda C Petersen3
1Institute of Oral Biology, University of Oslo, Oslo, Norway. sudhanshu.shekhar@odont.uio.no.
Insights
Antibiotic use in newborns, specifically piperacillin and tazobactam, reduces CD4+ and CD8+ T cell counts. This treatment also suppresses Th1 and Th17 immune responses to Streptococcus pneumoniae, impacting neonatal immunity.
Area of Science:
- Immunology
- Neonatal Medicine
- Pharmacology
Background:
- Antibiotics are frequently administered to neonates, yet their effects on developing T cell immunity are not fully understood.
- The study focuses on the impact of piperacillin-tazobactam on neonatal T cell responses to Streptococcus pneumoniae.
Purpose of the Study:
- To investigate how piperacillin and tazobactam affect neonatal CD4+ and CD8+ T cell immunity.
- To determine the influence of this antibiotic combination on T cell responses to Streptococcus pneumoniae in neonates.
Main Methods:
- Neonatal mice were treated with piperacillin and tazobactam or a saline control.
- Splenic and lung cells were isolated and stimulated in vitro with Streptococcus pneumoniae.
- T cell cytokine production (IFN-γ, IL-17A, IL-4) was analyzed using ELISA and flow cytometry.
Main Results:
- Piperacillin-tazobactam exposure led to decreased CD4+ and CD8+ T cell numbers in neonatal mouse spleens and lungs.
- Antibiotic-treated mice showed reduced production of IFN-γ (Th1) and IL-17A (Th17) cytokines upon S. pneumoniae stimulation.
- No significant alteration in IL-4 (Th2) production was observed, indicating a selective impact on T cell subsets.
Conclusions:
- Piperacillin and tazobactam treatment in neonatal mice impairs T cell numbers and suppresses Th1 and Th17 responses to S. pneumoniae.
- The findings highlight potential vulnerabilities in neonatal adaptive immunity following common antibiotic use.
- These results may inform the development of improved therapeutic strategies for neonatal infections.
Background:
Antibiotics are commonly used in human neonates, but their impact on neonatal T cell immunity remains poorly understood. The aim of this study was to investigate the impact of the antibiotic piperacillin with the beta-lactamase inhibitor tazobactam on neonatal CD4+ and CD8+ T cell responses to Streptococcus pneumoniae.
Methods:
Splenic and lung cells were isolated from the neonatal mice receiving piperacillin and tazobactam or saline (sham) and cultured with S. pneumoniae to analyze T cell cytokine production by ELISA and flow cytometry.
Results:
Antibiotic exposure to neonatal mice resulted in reduced numbers of CD4+/CD8+ T cells in the spleen and lungs compared to control mice. Upon in vitro stimulation with S. pneumoniae, splenocytes and lung cells from antibiotic-exposed mice produced lower levels of IFN-γ (Th1)/IL-17A (Th17) and IL-17A cytokines, respectively. Flow cytometric analysis revealed that S. pneumoniae-stimulated splenic CD4+ T cells from antibiotic-exposed mice expressed decreased levels of IFN-γ and IL-17A compared to control mice, whereas lung CD4+ T cells produced lower levels of IL-17A. However, no significant difference was observed for IL-4 (Th2) production.
Conclusions:
Neonatal mice exposure to piperacillin and tazobactam reduces the number of CD4+ and CD8+ T cells, and suppresses Th1 and Th17, but not Th2, responses to S. pneumoniae.
Impact:
Exposure of neonatal mice with a combination of piperacillin and tazobactam reduces CD4+/CD8+ T cells in the spleen and lungs. Antibiotic exposure suppresses neonatal Th1 and Th17, but not Th2, responses to Streptococcus pneumoniae. Our findings may have important implications for developing better therapeutic strategies in the neonatal intensive care unit.
